Patients suffering from manic, depressive, schizoaffective, and anxiety-related disorders are longitudinally evaluated and treated. Double-blind, placebo-controlled clinical trials are employed. Classical neurotransmitters and their metabolites, as well as hormones and peptides implicated in the regulation of mood and behavior, are measured in blood and CSF of patients to assess their relationship to normal and pathological behavior. Alterations in cognitive function, neurophysiology, and biochemistry are explored in relationship to predictors and mechanisms underlying clinical response to treatments of mood and anxiety disorders with agents including anticonvulsants, noradrenergic receptor agonists, sleep deprivation, lithium carbonate, and other antidepressant modalities. Ongoing clinical trials with carbamazepine indicate it is a new and useful alternative to lithium carbonate for the acute and prophylactic treatment of manic-depressive illness. The biochemical and physiological effects of carbamazepine are being explored in the hope they will not only elucidate its mechanisms of action in affective illness, but provide a basis for better understanding the processes underlying affective dysregulation. Animal models of electrical kindling and stimulant-induced behavioral sensitization are explored in order to examine mechanisms underlying progressive changes in behavioral pathology.